This invention relates generally to growth factors and more specifically, to the influence of transforming growth factor-β on excessive extracellular matrix production.
Various pathologies are characterized by a deleterious accumulation of extracellular matrix materials. For example, in progressive glomerular disease, extracellular matrix accumulates in the glomerulus or the glomerular basement membrane, eventually causing end-stage disease and uremia. Similarly, adult respiratory distress syndrome (ARDS) involves the accumulation of matrix materials in the lung while cirrhosis of the liver is characterized by deleterious matrix accumulation in the liver.
Extracellular matrix is a mixture of proteoglycans, glycoproteins and collagens assembled into a complex superstructure. Although a variety of immunologic, hemodynamic and toxic factors have been used experimentally to induce glomerular disease, none of these factors has been shown to directly influence synthesis or degradation of extracellular matrix components. Thus it seems likely that there is another intervening process between acute cell injury and buildup of glomerular extracellular matrix.
There thus exists a need to determine the factors which regulate deleterious accumulation of matrix components in pathological states such as kidney disease. Further, there exists a need to control such agents so as to prevent, limit or treat pathogenic conditions which include inappropriate matrix accumulation. The present invention satisfies these needs and provides related advantages as well.